Sodium Bicarbonate → HCID 86344810, compound

HRID 711178Notes

Reaction equation

HRID 711178 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:35][C:36]([NH:38][C@@H:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C@H:42]([O:49][C:50]3[CH:51]=[CH:52][C:53]4[N:54]([C:56]([N:59]5[CH2:64][CH2:63][CH2:62][CH2:61][C@@H:60]5[CH3:65])=[N:57][N:58]=4)[CH:55]=3)[CH2:41][CH2:40]2)=[O:37])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][Si](C(C)C)(C(C)C)C(C)C)=[C:12]([CH2:27][N:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:84](=O)([OH:86])[O-:85].[Na+]>C1COCC1.C(Cl)Cl>[CH:84]([OH:86])=[O:85].[C:1]([C:5]1[CH:6]=[C:7]([NH:35][C:36]([NH:38][C@@H:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C@H:42]([O:49][C:50]3[CH:51]=[CH:52][C:53]4[N:54]([C:56]([N:59]5[CH2:64][CH2:63][CH2:62][CH2:61][C@@H:60]5[CH3:65])=[N:57][N:58]=4)[CH:55]=3)[CH2:41][CH2:40]2)=[O:37])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([CH2:27][N:28]3[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 123957994HCID 123957994, compound

Product 1

HCID 86344810HCID 86344810, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of Intermediate 61g (18 mg, 0.02 mmol) in THF (0.10 mL) was treated with tetrabutylammonium fluoride (1M in THF, 0.10 mL, 0.10 mmol) and the mixture was heated to 50° C. for 2 h. The mixture was diluted with DCM and a saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by HPLC (Method 6; 5-95% MeCN in H2O, 0.1% HCO2H over 25 mins) to give the title compound (5 mg, 33%). LCMS (Method 5): Rt 3.52 min, m/z 747.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.4 Hz), 1.26 (9H, s), 1.44-1.56 (2H, m), 1.61-1.73 (2H, m), 1.74-1.98 (4H, m), 1.99-2.12 (2H, m), 2.13 (3H, s), 2.25-2.37 (3H, m), 2.37-2.49 (5H, m, obscured by DMSO), 2.86-2.95 (1H, m), 3.12-3.19 (1H, m, obscured by water), 3.20-3.44 (1H obscured by water), 3.64 (2H, s), 4.77-4.86 (1H, m), 5.51 (1H, t, J=4.4 Hz), 6.28 (1H, s), 6.81-6.85 (1H, m), 7.05 (1H, d, J=8.6 Hz), 7.15-7.21 (3H, m), 7.24-7.30 (2H, m), 7.30-7.39 (2H, m), 7.63 (1H, d, J=10.2 Hz), 7.69 (1H, d, J=1.7 Hz), 7.95 (1H, s), 8.36 (0.1H, s).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was then extracted with DCM (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by HPLC (Method 6; 5-95% MeCN in H2O, 0.1% HCO2H over 25 mins)

Sources & evidence

ORD record
ord-2a2ead0545be4ae29e7ea69feb6c63d3
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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